The sermon by Bro. John Eko focuses on the importance of setting one's affections on godly matters rather than worldly distractions, emphasizing that the affections of Christians should be directed towards God, Jesus, the Bible, the church, fellow believers, and the lost. It warns against the dangers of self-love, sinful pleasures, and the pursuit of money, which can lead to spiritual downfall. Ultimately, the message highlights the powerful impact of our affections on our eternal destination and encourages believers to make conscious choices to prioritize their spiritual lives.